Since a majority of a pharmaceutical agent is flown from eyes to nose when the pharmaceutical agent is administered to eyes, study to stay a pharmaceutical agent on the surfaces of eyes as long time as possible by increasing the viscosity of a preparation has been progressed. In order to increase the viscosity of a preparation, a polymer compound is generally added. However, when the viscosity of a preparation is increased, there arises dispersion in an administration amount, and such a defect is caused that administration of a constant amount becomes difficult.
The viscosity of an aqueous solution of a polymer compound is generally lowered when a temperature is arisen. However, an aqueous solution of methylcellulose (MC), hydroxypropylmethylcellulose, poly(vinyl alcohol) or the like has the characteristic that it is gelled and the viscosity is increased at a certain temperature or a higher temperature.
In Japanese Patent No. 2729859, a gelation temperature was successfully lowered to a temperature around a body temperature of human (40° C. or less) by adding 1.2 to 2.3 w/v % of citric acid and further 0.5 to 13 w/v % of polyethylene glycol (PEG) into 0.2 to 2.1 w/v % of methylcellulose, the 2 w/v % aqueous solution of which has a viscosity 13 to 12000 mPa·s at 20° C. Since this preparation has the characteristics that the preparation is liquid before administration, so that is easy to be administered. In addition the preparation is gelled by a body temperature after administration to increase the viscosity, so that the preparation has the advantages that retention effect of a pharmaceutical agent at the administration site is improved and the bioavailability (BA) of a pharmaceutical agent is improved.
The present inventor tried to apply a thermally gelling preparation described in Japanese Patent No. 2729859 to new quinolone antibacterial agents including ofloxacin which is a synthetic antibacterial agent. However, when an ophthalmic solution of ofloxacin prepared according to the thermally gelling composition described in Japanese Patent No. 2729859 and a commercially available aqueous ofloxacin ophthalmic solution were compared, there was no difference in intraocular dynamic of ofloxacin between both ophthalmic solutions.